MCAS - Symptoms, Causes, Diagnosis and Treatment - Dominick Hussey

Mast Cell Activation Syndrome – Symptoms, Causes, Diagnosis and Treatment

Mast cell activation syndrome (MCAS) is a type of mast cell activation disorder (MCAD).

MCAD is the term for describing the whole spectrum of diseases of the mast cell.

There are two main types of primary mast cell diseases including:

  1. Mastocytosis – A rare mast cell activation disorder caused by the presence of too many mast cells and mast cell precursors. People affected by mastocytosis are susceptible to itching, hives, and anaphylactic shock, caused by the release of histamine from mast cells.
  2. Allergic-type phenomena –  Like allergies, urticaria, angioedema, and anaphylaxis.

There is a third type of MCAS where we observe inappropriate activation of the mast cells, where we cannot describe it as either Mastocytosis or an allergic-type phenomenon. We label this type of MCAD under the MCAS banner.

Read on to learn about the symptoms, diagnosis, causes, testing and treatment of MCAS.

What are the typical symptoms and systems affected by MCAS?

MCAS may affect virtually any system in the body. So by definition, MCAS may cause a multitude of different symptoms.

Neurological System

Neurologically, you may see symptoms of fatigue and cognitive dysfunction that a lot of people describe as “brain fog.”

There may be a motor and sensory neurologic issues.

And if the central nervous system is affected, there could be psychiatric issues including anxiety and depression.

Cardiovascular system

MCAS may affect the cardiovascular system with all sorts of autonomic related issues including:

  • Variability in pulse and blood pressure
  • Palpitations or Tachycardia or increased heart rate

Musculoskeletal system

MCAS may cause a lot of muscle pain, which is diffusely migratory. There may also be bone issues including osteopenia and osteoporosis.

Gastrointestinal (GI) System

MCAS can cause all sorts of issues in the GI tract including acid reflux, nausea, vomiting, and alternating diarrhea and constipation.

The Skin

We find mast cells predominantly at environmental interfaces on the outside of the body where they’re best positioned to serve out their principal role and defence. As such we see many skin issues with MCAS including rashes as well as nail and hair problems.

When you think about the biology of this, where do mast cells reside in the body? Well, there are present in every vascularized tissue, but they dominantly site themselves at the environmental interfaces and also perivascular sites. So that’s

Respiratory System

The lungs are another example of an environmental interface found in the body. As such, patients with MCAS can describe intermittent problems with shortness of breath, and sometimes wheezing.

Genitourinary (GU) System

The GU tract is another environmental interface. So MCAS patients may experience irritation and pain in the urinary tract.

Immune System

MCAS can reduce the function of the Immune system so leading to a wide range of possible consequences, including:

  • Increased susceptibility to infection
  • Increased difficulty with healing from infections and wounds
  • Increased risk for malignancies
  • Increased risk for autoimmune disease

We could go on to the other systems in the body, but I think you get the point that it’s just a bewilderingly vast array of potential symptoms.

Diagnosis of MCAS

The sheer number of different symptoms and the fact that each person can have different symptom picture makes diagnosing MCAS extremely difficult.

According to MCAS expert Dr Lawrence Afrin, most patients who are ultimately found to have MCAS have been searching for help with their symptoms for a very long time, typically for decades.

Cause of MCAS

At present, there are no scientifically validated cause for MCAS only possible theories.

One theory originates from researchers at the University of Bonn Germany. They suggest that MCAS patients may have mutations in the controlling elements of the mast cells. This opinion has not yet been verified so we more research to understand the cause better.

Testing for MCAS

Currently, there is no single reliable laboratory test available for the diagnosis of MCAS. There are some tests available that collectively give a good indication of MCAS.

  • Serum Tryptase – Measuring tryptase levels in the serum can be very helpful in diagnosing mastocytosis. We usually see tryptase levels elevated at least double the upper limit of normal and quite often much higher than that in mastocytosis. However, in MCAS, tryptase is usually normal. Or if it is elevated, it’s just very slightly raised. So it is undoubtedly a good idea to check a serum tryptase when looking for MCAS.
  • Serum Chromogranin A – Chromogranin A (CgA) is a protein released from neuroendocrine cells. These are cells that secrete hormones in response to signals from the nervous system. When measuring serum CgA, you must rule out that the patient does not have heart or renal failure, has not taken proton Pump Inhibitors in the last three days and does not have neuroendocrine cancer. If you have ruled out all the above, then an elevated CgA level is a good indication of MCAS.
  • Plasma and Urine Prostaglandin D2 – Prostaglandin D2 is a significant prostaglandin produced by mast cells.
  • Plasma heparin – Heparin is a compound occurring in the liver and other tissues that inhibits blood coagulation. According to Dr Lawrence, Afrin plasma heparin is a helpful, sensitive and specific test for MCAS.
  • 2,3-Dinor-11beta-prostaglandin F2 alpha – 2,3-Dinor-11beta-prostaglandin F2 alpha is a metabolite of prostaglandin D2.
  • Urine Histamine
  • Urine N-methylhistamine
  • Urine Leukotriene E4

Treatment of MCAS

Because of the complicated nature of MCAS, I recommend a simple step by step approach to treatment.

Step one: Identify and avoid the triggers

Before looking for the underlying cause of MCAS, it is vital to reduce any symptoms. The first part of this is to identify and withdraw any triggers. Typical triggers include high histamine foods so following a low histamine elimination diet is useful. A low Fodmap diet may also be worth trying as it has been shown to lower histamine levels in the body. For my clients, I tend to start with the low Fodmap diet. If symptoms do not reduce to a manageable level, then we try a low fodmap low histamine diet.

Step two: Identify an optimal antihistamine regimen

The second part of controlling symptoms is to find an optimal antihistamine regimen. There are two types of antihistamines you can try, medications and supplements.


If symptoms are severe, it may be necessary to use antihistamine medications. There are two types of antihistamine medications, H1 and H2 blockers.

H1 Blockers

H1 antagonists, also called H1 blockers, are a class of medications that block the action of histamine at the H1 receptor, helping to relieve allergic reactions. There are two types of H1 blockers, sedating and non-sedating. Since fatigue is such a common symptom in MCAS, it is better to use a non-sedating kind of H1 blocker. Examples of non-sedating H1 blockers include Allegra and Claritin.

H2 Blockers

H2 antagonists, sometimes referred to as H2RA and also called H2 blockers, are a class of medications that block the action of histamine at the histamine H2 receptors of the parietal cells in the stomach. They are typically used to reduce the production of acid in the stomach. Examples of H2 Blockers include Pepcid and Zantac.

When treating MCAS, you will often need a combination of an H1 and H2 blocker. There is no easy way to find the right combination except through a patient step by step trial and error approach. At this point, I would highly recommend you try this under the supervision of your doctor or trusted healthcare practitioner.

Natural Antihistamines

Natural antihistamines that have been shown to reduce histamine levels in the body include:

Step Three: Identifying and treating the cause

As I mentioned above, there is no known cause fore MCAS only theories.

In my clinical practice, I see a strong association between the presence of SIBO and excess histamine. This observation may explain why a low fodmap diet can be a useful tool for reducing a high histamine body load and reducing symptoms.

Regarding cause, I see some parallels with MCAS and true Fibromyalgia. Research has shown a possible link between fibromyalgia and childhood trauma. There has also been some research looking at an association between histamine and stress.

Based on the above observations I suggest a two-step approach for looking at the underlying cause of MCAS.

Step One – Looking for Infections

Assuming that we have already removed any food triggers from the diet then the next step would be to look for any gut infections in particular SIBO. You can do this by using a Lactulose Breath Test.

Step Two – Identifying and Resolving any Past Emotional Traumas

There are some treatment modalities that I recommend and may help with past emotional trauma, some are scientifically validated and some not.



Energy Healing


Mindfulness Training


This article is not intended to provide medical advice, diagnosis or treatment.

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